Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial / 中华医学杂志(英文版)

BACKGROUND@#LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.@*METHODS@#We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels.@*RESULTS@#On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]).@*CONCLUSION@#LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT04563936.

Risk modeling based on HER-2 related genes for bladder cancer survival prognosis assessment / 北京大学学报(医学版)

OBJECTIVE@#To investigate the correlation between the human epidermal growth factor receptor-2-related genes (HRGs) and survival prognosis of bladder cancer and to construct a predictive model for survival prognosis of bladder cancer patients based on HRGs.@*METHODS@#HRGs in bladder cancer were found by downloading bladder tumor tissue mRNA sequencing data and clinical data from the cancer genome atlas (TCGA), downloading HER-2 related genes from the molecular signatures database (MsigDB), and crossing the two databases. Further identifying HRGs associated with bladder cancer survival (P < 0.05) by using single and multi-factor Cox regression analysis and constructing HRGs risk score model (HRSM), the bladder cancer patients were categorized into high-risk and low-risk groups accor-ding to the median risk score. Survival analysis of the patients in high- and low-risk groups was conducted using R language and correlation of HRGs with clinical characteristics. A multi-factor Cox regression analysis was used to verify the independent factors affecting the prognosis of the patients with bladder cancer. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) of HRSM was calculated, and a nomogram was constructed for survival prediction of the bladder cancer patients. Analysis of HRSM and patient immune cell infiltration correlation was made using the TIMER database.@*RESULTS@#A total of 13 HRGs associated with patient survival were identified in this study. Five genes (BTC, CDC37, EGF, PTPRR and EREG) were selected for HRSM by multi-factor Cox regression analysis. The 5-year survival rate of the bladder cancer patients in the high-risk group was significantly lower than that of the patients in the low-risk group. High expression of PTPRR was found to be significantly and negatively correlated with tumor grade and stage by clinical correlation analysis, while EREG was found to be the opposite; Increased expression of EGF was associated with high grade, however, the high expression ofCDC37showed the opposite result. And no significant correlation was found between BTC expression and clinical features. Correlation analysis of HRSM with immune cells revealed a positive correlation between risk score and infiltration of dendritic cells, CD8+T cells, CD4+T cells, neutrophils and macrophages.@*CONCLUSION@#HRGs have an important role in the prognosis of bladder cancer patients and may serve as new predictive biomarkers and potential targets for treatment.

The application potential of a modified wireless intelligent capsule cystoscope for dynamic detection of porcine bladder mucosa / 中华泌尿外科杂志

Objective:To develop an improved wireless intelligent capsule cystoscope (WCE)for dynamic detection of bladder mucosa in a pig model.Methods:The WCE was introduced into a healthy experimental pig that under general anesthesia via urethra by applying an improved device. Multi-angle images of the bladder mucosa were then obtained by controlling the position of capsule cystoscope with an external magnetic field system. The shutter speed of the WCE was 2.5 fps and was automatically converted to 1.5 fps 30 minutes after initiation. The Vue software was utilized to download the shoot pictures which were former received by a computer via wireless transmission. The pig was roused and sent to the pigpen, without limitations in moving. The improved WCE was connected with a 2 cm thread. 12 hours later, the dilated sheath was inserted again, and the capsule was removed by a foreign body forceps under observation of a ureteroscopy.Results:The WCE was successfully placed and removed from the pig's bladder with the application of the improved devices. Over 20 thousand images that with 60K pixels of bladder mucosa were captured by the WCE at various angles within 12 hours, which revealed the process of urine filling and excreting in a time-dependent way. No notable adverse effects (bleeding, urinary tract injury, etc) were noted during the process of cystoscope placement, image acquisition, transmission, and removal.Conclusion:This study developed a novel WCE that could dynamically, intelligently and accurately monitor all aspects of the pig bladder mucosa, and has preferable application prospect.

4-1BB antibody enhances cytotoxic activity of natural killer cells against prostate cancer cells via NKG2D agonist combined with IL-27.

Aims: To enhance the cytotoxicity of natural killer (NK) cells against prostate cancer cells via NKG2D agonist, with 4-1BB antibody and IL-27 combination. Materials & methods: FACS was used to detect degranulation and cell surface receptors in NK cells isolated from healthy donors. Cytokine concentrations were measured using ELISA. NK-cell cytotoxicity was analyzed using Cell Counting Kit-8. Results: NKG2D agonist, 4-1BB antibody and IL-27 combination treatment improved the activating receptor expression and IFN-γ and TNF-α secretion but decreased the suppressive receptor CD158a expression and IL-10 secretion in NK cells. The combined treatment enhanced NK-cell cytotoxicity against both PC3 and DU145 cells with concurrent enhanced STAT3 activation. Conclusion: 4-1BB antibody and IL-27 improved NKG2D agonist function in NK cells against prostate cancer cells.

Efficacy and Adverse Reaction of Tislelizumab Combined with Chemotherapy on Urothelial Carcinoma / 肿瘤防治研究

Objective To evaluate the efficacy and safety of tislelizumab combined with chemotherapy in the treatment of urothelial carcinoma in the real word. Methods We enrolled 32 patients with urothelial carcinoma who were treated with tislelizumab and chemotherapy (gemcitabine/cisplatin or paclitaxel). The incidence of treatment-related adverse reactions during treatment and the efficacy evaluation were statistically analyzed. Results All patients were divided into two groups: 15 patients in the tislelizumab combined with paclitaxel group and 17 patients in the tislelizumab combined with GC group. Among 24 efficacy-evaluable patients, the ORR was 54.2% and the DCR was 83.3%. The ORR were 50.0% and 58.3%, and the DCR were 75.0% and 91.7% in the tislelizumab combined with paclitaxel group and the tislelizumab combined with GC group respectively. Common treatment-related adverse reactions included anemia (56.3%), loss of appetite (53.1%) and skin pruritus (50.0%). The grade 3-4 treatment-related adverse events occurred in 21.8% of patients. Common immune-related adverse reactions included skin toxicity (53.1%) and immune colitis (9.4%). Conclusion Tislelizumab combined with chemotherapy on urothelial cancer has significant curative effect, safety and controllability, but attention should be paid to immune-related adverse reactions.

The value of combined detection of serum neurogranin and hypoxia-inducible factor-1α on the prognosis in patients with severe craniocerebral trauma / 中国医师进修杂志

Objective:To investigate the value of combined detection of serum neurogranin (NG) and hypoxia-inducible factor-1α (HIF-1α) in patients with severe craniocerebral trauma.Methods:Ninety-seven patients with severe craniocerebral trauma from June 2018 to March 2020 in Jinshan Branch of Shanghai Sixth People′s Hospital were selected. According to the Glasgow outcome score (GOS), 97 patients were divided into good prognosis group (GOS>3 scores, 46 cases) and poor prognosis group (GOS ≤ 3 scores, 51 cases). The NG, HIF-1α, Glasgow coma score (GCS), acute physiology and chronic health status score Ⅱ (APACHE Ⅱ) were compared between 2 groups. The independent risk factors of prognosis in patients with severe craniocerebral trauma were analyzed by multivariate Logistic regression analysis. The diagnostic efficacy of NG and HIF-1α on poor prognosis in patients with severe craniocerebral trauma was analyzed by receiver operating characteristic (ROC) curve. The correlation between serum NG, HIF-1α and APACHE Ⅱ in patients with severe craniocerebral trauma was analyzed by Pearson analysis.Results:The GCS in good prognosis group was significantly higher than that in poor prognosis group: (6.50 ± 1.74) scores vs. (4.76 ± 0.78) scores, the NG, HIF-1α and APACHE Ⅱwere significantly lower than those in poor prognosis group: (696.98 ± 158.96) ng/L vs. (875.92 ± 188.52) ng/L, (34.72 ± 13.98) μg/L vs. (51.29 ± 14.17) μg/L and (15.69 ± 3.45) scores vs. (22.58 ± 6.45) scores, and there were statistical differences ( P<0.01). Multivariate Logistic regression analysis result showed that the NG, HIF-1α, APACHEⅡ, GCS and type of craniocerebral trauma were independent risk factors on the prognosis in patients with severe craniocerebral trauma ( P<0.05 or<0.01). ROC curve analysis result showed that the AUC of NG and HIF-1αNG and HIF-1α combined detection to assess the poor prognosis in patients with severe craniocerebral trauma was significantly higher than NG and HIF-1α alone detection (0.873 vs. 0.772 and 0.821, Z = 2.276 and 1.949, P<0.05). Pearson correlation analysis result showed that APACHE Ⅱ was positive correlation with serum NG and HIF-1α in severe craniocerebral trauma patients with poor or good prognosis ( r = 0.852 and 0.889, P<0.01; r = 0.717 and 0.851, P<0.01). Conclusions:The combined detection of serum NG and HIF-1α can be used as an evaluation index for the prognosis in patients with severe craniocerebral trauma, which helps to determine the severity of craniocerebral trauma and has great value for clinical diagnosis and treatment.

Study on the influence of "Internet+" case teaching model on critical thinking of nursing interns / 中国实用护理杂志

Objective@#To explore and analyze the intervention effect of two different case teaching methods on critical thinking of nursing interns.@*Methods@#from July 2016 to July 2018, a total of 62 nursing students in a three grade hospital in Chongqing were selected. They were divided into control group (29) and intervention group (33) according to their internship years. The control group received routine case teaching method, while the intervention group adopted the "Internet+" case teaching method to carry out clinical teaching.@*Results@#Nursing students in the intervention group were significantly better than those in the control group in seeking truth, open thinking, systematization ability, analytical ability, self-confidence, thirst for knowledge and maturity (t=3.978-6.875, P<0.05). Nursing students in the critical thinking grade distribution intervention group were higher than those in the control group (t=-6.522--2.202, P<0.05). In clinical decision-making ability, problem-finding ability, goal-setting ability, decision-making ability, implementation decision-making ability and evaluation feedback were also higher than those in the control group (P<0.05). The ability was higher than that of the control group (χ2=7.922, P<0.05).@*Conclusion@#case teaching based on "Internet+" can better improve the clinical thinking method of nursing students, enhance the critical thinking level and clinical decision-making ability of nursing students, and improve the quality of clinical teaching. It is worthy of popularization and application in clinical practice.

Study on the influence of "Internet+" case teaching model on critical thinking of nursing interns / 中国实用护理杂志

Objective To explore and analyze the intervention effect of two different case teaching methods on critical thinking of nursing interns. Methods from July 2016 to July 2018, a total of 62 nursing students in a three grade hospital in Chongqing were selected. They were divided into control group (29) and intervention group (33) according to their internship years. The control group received routine case teaching method, while the intervention group adopted the "Internet+" case teaching method to carry out clinical teaching. Results Nursing students in the intervention group were significantly better than those in the control group in seeking truth, open thinking, systematization ability, analytical ability, self-confidence, thirst for knowledge and maturity (t=3.978-6.875, P<0.05). Nursing students in the critical thinking grade distribution intervention group were higher than those in the control group (t=-6.522--2.202, P< 0.05). In clinical decision-making ability, problem-finding ability, goal-setting ability, decision-making ability, implementation decision-making ability and evaluation feedback were also higher than those in the control group (P<0.05). The ability was higher than that of the control group (χ2=7.922, P<0.05). Conclusion case teaching based on "Internet+" can better improve the clinical thinking method of nursing students, enhance the critical thinking level and clinical decision-making ability of nursing students, and improve the quality of clinical teaching. It is worthy of popularization and application in clinical practice.

Two cases of aldosterone-and cortisol-producing adenoma / 中华内分泌外科杂志

More and more cases of aldosterone-and cortisol-producing adenoma (A/CPA) have been reported in recent years.In order to further understand the clinical characteristics of patients with A/CPA,we report 2 cases of A/CPA treated in our hospital,and analyzes them in combination with domestic reports.We recommend that clinicians routinely perform Low Dose Dexamethasone Suppression Test on every primary aldosteronism patient prior to adrenal vein sampling (AVS) or adrenal adenoma surgery to rule out the possibility of Cushing's syndrome so as to avoid the wrong judgment of AVS results and avoid adrenal hypofunction or adrenal crisis after operation.

Prostaglandin E2 Inhibits Prostate Cancer Progression by Countervailing Tumor Microenvironment-Induced Impairment of Dendritic Cell Migration through LXRα/CCR7 Pathway.

Migration and homing of dendritic cells (DCs) to lymphoid organs are quite crucial for T cell-induced immune response against tumor. However, tumor microenvironment can make some tumor cells escape immune response by impairing DC migration. Prostaglandin E2 (PGE2) plays important roles in initiating and terminating inflammatory responses. In this study, we investigated whether PGE2 could inhibit murine prostate cancer progression by countervailing tumor microenvironment-induced impairment of dendritic cell migration. We found that murine prostate cancer cell line RM-1-conditioned medium impaired chemotactic movement of marrow-derived DCs and splenic cDCs toward CC chemokine receptor-7 (CCR7) ligand CCL19 in vitro and migration to draining lymph gland in vivo. Meanwhile, it also induced LXRα activation and CCR7 inhibition on maturing DCs. However, the treatment of PGE2 rescued this impairment of DC migration with upregulation of CCR7 and inhibition of LXRα. Further, it was observed that PGE2 also increased MMP9 expression and activated Notch1 signaling on DCs. In RM-1-bearing mouse model, PGE2 treatment was identified to inhibit tumor growth and induce more tumor-infiltrating T cells and CD11c dendritic cells in tumor sites. Therefore, our findings may demonstrate a new perspective for therapeutic interventions on prostate cancer immunoescape.

The clinical efficacy of laparoscopy vs open choledocholithotomy plus T tube drainage in treating cholangiolithiasis / 中华普通外科杂志

Objective To compare the clinical efficacy of laparoscopic vs open choledocholithotomy plus T tube drainage for the treatment of extra-and intrahepatic cholangiolithiasis.Methods 300 patients with cholangiolithiasis undergoing surgical treatment in the Department of Hepatobiliary Surgery,Guizhou Provincial People's Hospital,from January 2012 to December 2016 were evaluated.Patients were divided into laparoscopic lithotomy of common bile duct plus T tube drainage group (n =120)and open surgery (n =180).Results The difference was not statistically significant in operation time (237 ±32) min,(t =0.671,P =0.504),operation success rate (100％),primary cure rate (81.7％),(x2 =0.400,P =0.531),residual stone rate (18.3％),(x2 =0.400,P =0.531),hospitalization costs (26 ±4) × 103 RMB,(t =0.981,P =0.329),perioperative complications including bile leakage(0),biliary bleeding (0),abdominal hemorrhage (0),acute cholangitis (0),(x2 =0.669,P =1.000),abdominal infection (0) and incisional infection (0),(x2 =1.342,P =0.518) and late complications including biliary stricture(0) and stone recurrence (11.7％),(x2 =0.022,P =1.000) between the two groups.While intraoperative blood loss (25 ± 14)ml,(t =-7.191,P =0.000),postoperative recovery time of gastrointestinal function (1.8 ± 0.6) d,(t =-5.847,P =0.000),postoperative hospital stay (10.1 ± 0.3) d,(t =-3.145,P =0.000),postoperative incision liquefaction (0),(x2 =26.415,P =0.000) were in favor of laparoscopy group with statistically significant difference.Conclusions For the treatment of extra-and intrahepatic cholangiolithiasis,it was feasible and effective for laparoscopic lithotomy of common bile duct plus T tube drainage.

Clinical analysis on 64 cases of testicular torsion and literature review / 重庆医学

Objective To investigate the clinical characteristics of testicular torsion,and to provide the strategies for its early diagnosis and timely therapy.Methods The clinical data in the patients with testicular torsion diagnosed by surgical exploration from March 2011 to December 2016 were reviewed.The clinical characteristics were compared between the testis-preserving group and testis-resection group.The latest advances in the diagnosis and treatment of testicular torsion were summarized.Results A total of 64 cases of testicular torsion were included in this study.There were 27 cases in the testicle-preserving group with the age range of(8-40) years old,the average age was(19.00±5.28) years old,the onset time range was(1-24) h,the average time was (8.78 ± 6.73) h;the intraoperative sper matic cord twist range was (180-540) ° and average (290.00 ±103.92) °;6 cases were misdiagnosis with the misdiagnosis rate of 22.22 ％.There were 37cases in the testicle-resection group with the age range of(10-34),the average age was(19.00 ± 7.45) years old;the onset time range was (12-168) h,the average time was(66.92 ± 47.01) h,the intraoperative spermatic cord twist range was(180-720)° and average(457.00± 168.88)°;22 cases were misdiagnosed with the misdiagnosis rate of 59.46 ％.The onset time,spermatic cord twist degree and misdiagnosis rate had statistically significant difference between the two groups(P＜0.05).Conclusion Testicular torsion is an important urinary emergency condition which can not be ignored.Timely and effective treatment is the key to save the testicles.

Exercise overcome adverse effects among prostate cancer patients receiving androgen deprivation therapy: An update meta-analysis.

BACKGROUND: Prostate cancer (PCa) patients initiating androgen deprivation therapy (ADT) are suffering from adverse effects; exercise has been proposed as a treatment to relieve adverse effects of ADT, available meta-analysis has proved exercise improves quality of life, and therapy caused fatigue; recently, some high-quality trials have been conducted in order to get more assessment; we conduct an updated meta-analysis to evaluate feasibility that exercise relieves adverse effects in PCa patients initiating ADT. MATERIALS AND METHODS: A systematic article search was performed from Cochrane Library, MEDLINE, EMBASE, and PubMed databases up to March 10, 2017. Outcomes included changes in body composition, physical function, bone health and cardiometabolic changes. We conduct subgroup analysis to analyze the duration and type of exercise correlated with the effect and calculated using standard mean difference (SMD) and corresponding 95% confidence intervals (CI). RESULT: Fifteen studies involving 1135 patients were included in our meta-analysis, and significant positive effects were found in body strength (leg press (SMD: 0.78 (95%CI: 0.57-0.99, P <.00001, I = 0%)), chest press (SMD: 0.71 (95%CI: 0.50-0.92, P <.00001, I = 0%)), exercise tolerance (VO2 peak SMD: 0.35 (95%CI: 0.04-0.66, P = .03, I = 0%) in 6 months and SMD: 0.59 (95%CI: 0.16-1.03, P = .007, I = 0% over 6 months)), fatigue (SMD: 0.84 (95%CI: -1.43 to 3.10, P = .85, I = 51%) in 6 months and SMD: -9.3 (95%CI: -16.22 to -2.39, P = .0030, I = 49%) over 6 months)), ADT-caused obesity (body mass index SMD: -0.33 (95%CI: -0.55 to -0.12, P = .002, I = 38% in 6 months and SMD: -0.59 95%CI: -1.02 to 0.17, P = .006, I = 25% over 6 months)), and sex function (SMD: 0.66 (95%CI: 0.35-0.97, P <.00001, I = 2%). There were no evidence of benefit for cardiometabolic changes and bone health. No systematic difference was observed between resistance exercise training (RET) and aerobic exercise training (AET) in ADT-caused obesity, fatigue, and exercise tolerance CONCLUSION:: Exercise can significantly improve the upper and lower muscle strength, increase exercise tolerance, help PCa patients receiving ADT control their body fat mass, BMI, and keep the sex function. ADT-related fatigue is correlated with exercise duration time. No differences were observed in LBM, bone mineral density, and any other metabolic blood markers. Available data show that there is no difference between AET and RET.

Liver X receptor activation inhibits PC-3 prostate cancer cells via the beta-catenin pathway.

BACKGROUND: Liver X receptors (LXRs) are nuclear receptors family of ligand-dependent transcription factors that play a crucial role in regulating cholesterol metabolism and inflammation. Recent studies show that LXR agonists exhibit anti-cancer activities in a variety of cancer cell lines including prostate. To further identify the potential mechanisms of LXRα activation on prostate cancer, we investigated the effect of LXR agonist T0901317 on PC3 prostate cancer cell and in which activity of beta-catenin pathway involved. METHODS: Prostate cancer PC3 cells were transfected with LXR-a siRNA and treated with LXR activator T0901317. qRT-PCR and western blot were used to detect the LXR-a expression. beta-catenin, cyclin D1 and c-MYC were analyzed by western blot. Cell apoptosis was examined by flow cytometry and Cell proliferation was assessed by Cell Counting Kit-8 assay. Cell migration was detected by Transwell chambers. RESULTS: Data showed that T0901317 significantly inhibited PC3 cell proliferation as well as invasion and increased apoptosis in vitro. Furthermore, we found that LXRα activation induced the reduction of beta-catenin expression in PC3 cells, and this inhibitory effect could be totally abolished when cells were treated with LXRα. Meanwhile, the expression of beta-catenin target gene cyclin D1 and c-MYC were also decreased. CONCLUSIONS: This study provided additional evidence that LXR activation inhibited PC-3 prostate cancer cells via suppressing beta-catenin pathway.

Teaching practice and thinking of short-term skill training in urology / 中华医学教育探索杂志

With the deepening of the reform of public hospitals at the county level,as well as the development of medical technology personnel training and medical technology development in county hospitals,county hospitals should be able to make use of the latest technology to undertake the common diseases and frequently occurring diseases of county residents.So at present,the teaching hospitals affiliated to medical universities should carry out the short-term training of the latest special techniques in the training of the regular doctors.Department of Urology of the first Affiliated Hospital of Chongqing Medical University,in the 3 month training cycle,with improving the self-learning ability of the refresher doctors as the core,carried out the hand by hand teaching of small classes and introducing model teaching,which achieved good results.

Effects of cisplatin on autophagy and apoptosis and their correlation in bladder cancer cells / 基础医学与临床

Objective To identify whether cisplatin can induce autophagy of bladder cancer T24 cells and the possible mechanism, and to observe the relationship between outophagy and apoptosis.Methods MTT assay was applied to investigate the effects of various concentration of cisplatin( 0 , 10 , 20 and 40 μg/mL) on T24 survival.TEM was performed to detect the autophagosome formation .Western blot assay was used to analyze the expression changes of LC3-Ⅱ, P62 and extracellular signal-regulated kinase ( ERK1/2 ) and p-ERK at the protein level.The effects of autophagy on the survival and apoptosis of bladder cancer cells were investiga-ted.Results DDP observably inhibited proliferation of bladder cancer cells in a dose-dependent manner ( P<0.05), the 50% inhibiting concentration(IC50) was (30.3 ±2.4)μg/mL;DDP induced autophagy of bladder cancer cells, observably increased autophagosome induced by DDP; up-regulated expression levels of LC3-Ⅱproteins ( P<0.05 ) , down-regulated expression of P62 proteins ( P<0.05 );DDP increased the protein level of p-ERK (P<0.05); The inhibitor of ERK pathway U0126 inhibited DDP-induced autophagy, as evidenced by decrease in the expression of LC3-Ⅱproteins ( P<0.05 ) .After inhibition of autophagy by WTM in DDP-treated cells, cell viability was obviously decreased and apoptosis was increased (P<0.05);DDP combined with WTM observably enhanced cleavage of poly ADP-ribose polymerase 1 ( PARP-1 ) and cleaved-caspase-3 which is apop-tosis related proteins ( P<0.05 ) .Conclusions Autophagy can protect T24 cells against ciplatin-induced apop-tosis, the possible mechanism of autophagy is the ERK signaling pathway is activated .

Potent anti-prostate cancer immune response induced by dendritic cells transduced with recombinant adenoviruses encoding 4-1BBL combined with cytokine-induced killer cells.

AIM: To test the effect of dendritic cells (DCs) transduced with recombinant adenoviruses encoding 4-1BBL combined with cytokine-induced killer cells (CIKs) against prostate cancer. METHOD: Flow cytometry was used to detect the surface markers of the co-cultured cells, and cytotoxicity against prostate cancer cells in vitro as well as antitumor activities in vivo were observed. RESULTS: Our results showed that Ad-4-1BBL-transduced DCs could increase percentage of CD3(+)CD56(+) cells in CIKs, and CIKs co-cultured with Ad-4-1BBL-transduced DCs could augment the secretion of IL-12 and IFN-γ and decrease TGF-ß production. In addition, Ad-4-1BBL-transduced DCs enhanced the cytotoxicity of CIKs against prostate cancer and resulted in inhibition of tumor growth and tumor-bearing animals' survival. CONCLUSION: These results demonstrate that 4-1BBL-engineered DCs can improve CIKs cytotoxicity against prostate cancer cells.

Construction and identification of a recombinant lentivirus harboring expressing Mus musculus STAT3 gene / 重庆医学

Objective To construct recombinant lentivirus with the gene STAT3 of the Mus musculus,measure the expres-sion of STAT3,and conduct lentivirus packing and identification.Methods The mRNA of mouse myoblast was extracted and transformed into STAT3 cDNA by the special primer.then,STAT3 cDNA was amplified and reclaimed and inseted into pLVX-IRES-ZsGreen1 vector.Cleavage map and sequencing analysis were used for identification of the recombinant lentivirus vector (pLVX-IRES-ZsGreen1-STAT3).293 T cells were transfected with main vector pLVX-IRES-ZsGreen1-STAT3.and 48 h later, Western blott detected the expression of STAT3 protein.Lentiviral vectors were packaged and the titer was determined.Results The lentiviral vector plasmid pLVX-IRES-ZsGreen1-STAT3 was identified correctly by cleavage map and Co-transfection of 293 T cells with 48 h,the expression of STAT3 was significantly enhanced by western blot.And DNA sequencing analysis confirmed that STAT3 gene sequencing was exactly the same with that reported by genbank.Conclusion Lentiviral vector carrying STAT3 was successfnlly constructed and could express STAT3 with high efficiency,and can be used in further study.

Effect of oxidative stress-induced autophagy on proliferation and apopto-sis of MSCs / 中国病理生理杂志

AIM:To investigate whether oxidative stress is able to induce autophagy in mesenchymal stem cells (MSCs), and to explore the effects of autophagy on MSC proliferation and apoptosis under oxidative stress circumstance as well as the underlying mechanism for promoting the therapeutic effects of transplanted MSCs on treating diabetes mellitus e -rectile dysfunction ( DMED) .METHODS: Hydrogen peroxide ( H2 O2 ) was applied to simulate the oxidative stress cir-cumstance.The effects of H2 O2 at concentration of 0, 50, 100, 200, 400μmol/L on the viability of MSCs were tested by the method of Trypan blue exclusion and MTT assay respectively .The methods of MTT assay , Western blot and transmis-sion electron microscope ( TEM) were used to explore the effects of H 2 O2 on MSC apoptosis and autophagy .RESULTS:The proliferation of MSCs was obviously inhibited by H 2 O2 in a dose-dependent manner ( P<0.01) and the 50%inhibiting concentration (IC50) was (384.58 ±16.89) μmol/L.H2O2 induced apoptosis and autophay of MSCs .The proliferation rate of MSCs was suppressed by H 2 O2 significantly ( P<0.05 ) , with a further decline by blockade of autophagy ( P<0.05) whereas increased by blockade of apoptosis (P<0.05).H2O2 induced MSCs apoptosis obviously (P<0.05), with an augment of apoptosis ( P<0.05) by blockade of autophagy .Furthermore, the H2 O2 increased expression of cleaved caspase-3 and cleavage of poly ADP-ribose polymerase 1 (PARP1), Which were decreased by apoptosis blockade whereas were enhanced by blockade of autopahgy .CONCLUSION:Oxidative stress plays a dual role in MSC survival , which in-duces MSC apoptosis and autophagy .Moreover , blockade of autophagy intensifies MSC apoptosis .Therefore , it is a promis-ing method to ameliorate the effects of stem-cell based therapy on DMED by enhancing protective autophagy to increase the survival rate of transplanted MSCs against oxidative stress circumstance caused by diabetes mellitus .

Effects of transplantation with marrow-derived mesenchymal stem cells modified with survivin on renal ischemia-reperfusion injury in mice.

PURPOSE: To determine whether renal injury induced by ischemia-reperfusion (I/R) could be further improved by mesenchymal stem cells (MSCs) modified with survivin. MATERIALS AND METHODS: Lentiviral vectors were used to introduce the survivin gene into MSCs and the MSCs modified with survivin were transplanted into established mice models of renal I/R injury. Seven days later, serum creatinine (Scr) and blood urea nitrogen (BUN) were measured and the survival of MSCs was determined. Hematoxylin and eosin staining was used to assess renal pathological change. The expressions of hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF) in kidney tissue were detected by western blot. RESULTS: Mice transplanted with survivin-modified MSCs demonstrated good renal function recovery with Scr and BUN decline close to normal levels and improvement of renal I/R injury repair. Additionally, the survival of transplanted MSCs modified with survivin was enhanced and the expression of HGF and bFGF in kidney tissue was increased. CONCLUSION: Our results demonstrated that MSCs engineered to over-express survivin could enhance their therapeutic effect on renal I/R injury in mice, probably via the improved survival ability of MSCs and increased production of protective cytokines in ischemic tissue.